Design and conduct of phase II studies of targeted anticancer therapy: Recommendations from the task force on methodology for the development of innovative cancer therapies (MDICT)

Booth, Christopher M.; Calvert, A. Hilary; Giaccone, Giuseppe; Lobbezoo, Marinus W.; Eisenhauer, Elizabeth; Seymour, Lesley

doi:10.1016/j.ejca.2007.07.031

Cited by 65 publications

(34 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is contention as to whether biomarkers should be studied at all in Phase I and II studies as they may provide confusing data and make the studies more complex and expensive [58,59]. Certainly we advocate that biomarkers should be used to inform 'go/no go' decisions, and if pharmacodynamic biomarkers are identified to aid dosing, the results should not be ignored.…”

Section: Expert Opinionmentioning

confidence: 91%

Novel VEGF signalling inhibitors: how helpful are biomarkers in their early development?

Wood

Scott

Thomas

2009

Expert Opinion on Investigational Drugs

View full text Add to dashboard Cite

show abstract

Section: Expert Opinionmentioning

confidence: 91%

Novel VEGF signalling inhibitors: how helpful are biomarkers in their early development?

Wood

Scott

Thomas

2009

Expert Opinion on Investigational Drugs

View full text Add to dashboard Cite

show abstract

“…Recently multinomial phase II clinical trials have attracted a lot of attention for their application in cancer research (Dent et al, 2001, Freidlin et al, 2002, Goffin et al, 2011, Kocherginsky et al, 2009, Zee et al, 1999, and their use has been recommended by the Task Force on Methodology for the Development of Innovative Cancer Therapies of the NDDO Research Foundation (Booth et al, 2008). In this setting, indeed, a finer classification of the responses is needed since even when the cancer is not reduced but its dimension is kept stationary it might indicate that the drug is active (it has a cytostatic effect).…”

Section: Sequential Multinomial Estimation and Clinical Trialsmentioning

confidence: 99%

Boundary Crossing Random Walks, Clinical Trials, and Multinomial Sequential Estimation

Bibbona

Rubba

2012

Sequential Analysis

View full text Add to dashboard Cite

A sufficient condition for the uniqueness of multinomial sequential unbiased estimators is provided generalizing a classical result for binomial samples. Unbiased estimators are applied to infer the parameters of multidimensional or multinomial random walks that are observed until they reach a boundary. Clinical trials are shown to be representable within this scheme and an application to the estimation of the multinomial probabilities following multinomial clinical trials is presented.

show abstract

“…However, given that new, molecularly targeted agents may not invariably cause shrinkage of measureable tumor that is predictive of survival, there is increasing interest in understanding tumor volume as a continuous measure. This interest has led to the development of waterfall and spider plots as representative displays of individual patient tumor responses (32). Waterfall plots only show the best on-study change in tumor burden relative to baseline for each individual patient (Fig.…”

Section: Novel Endpoint Selections In the Context Of New Treatmentsmentioning

confidence: 99%

Making the Investigational Oncology Pipeline More Efficient and Effective: Are We Headed in the Right Direction?

LoRusso

Anderson

Boerner

et al. 2010

Clinical Cancer Research

View full text Add to dashboard Cite

Advances in our knowledge of the molecular mechanisms involved in cancer biology have contributed to an increase in novel target-specific oncology therapeutics. Unfortunately, clinical development of new drugs is an expensive and slow process, and the patient and financial resources needed to study the vast number of potential therapies are limited, requiring novel approaches to clinical trial design and patient recruitment. In addition, traditional efficacy endpoints may not be adequate to fully determine the therapeutic worth of the new classes of targeted agents. In this new era of drug development, it has become increasingly clear that new clinical trial design paradigms that examine nontraditional endpoints have become necessary to assist in prioritizing the development of the most promising agents. It is also vital that individual patient management be considered, and the subpopulations of patients most likely to derive benefit or experience harm from a new therapy be identified as early as possible. Phase I and II clinical trials allow investigators doing clinical research the opportunity to define these critical endpoints and subpopulations early on, before conducting large-scale randomized phase III clinical trials, which require an abundance of financial and patient resources. Clin Cancer Res; 16(24); 5956-62. Ó2010 AACR.Principles driving oncology clinical trial design were primarily developed in the 1970s, during the introduction of many cytotoxic anticancer therapies. In the current era of molecularly targeted therapy, these traditional clinical trial design principles and trial endpoints are being reconsidered. At present, the most widely accepted metric for therapeutic utility remains improvement in the length of survival. However, alternate endpoints, such as time to disease progression, durable overall response rate, or improvement in disease-related symptoms, may be more appropriate endpoints for different classes of agents being evaluated. A major goal in clinical cancer drug development is to obtain regulatory approval for an efficacious agent and, to reach this goal, developers must often evaluate a novel therapy through a pivotal randomized control trial (RCT). As the proliferation of molecularly targeted agents has increased, it is important to refine the critical steps that lead to RCT design and execution. This article proposes innovative approaches to earlier phase I and II trials, which may ultimately yield change in how we design, conduct, and inform RCTs as we advance into the next generation of oncology clinical trials. Phase I Trials: Novel Designs and Impact on Patient Outcome(s)Currently, nearly 900 novel cancer agents are undergoing investigation in more than 6,000 clinical trials (1-3). Owing to this large number of investigational agents, a critical lack of financial and patient resources significantly reduces the chances for adequate development of many of these agents. As a result, clinical drug developers require continual innovation in their approaches to best dete...

show abstract

Design and conduct of phase II studies of targeted anticancer therapy: Recommendations from the task force on methodology for the development of innovative cancer therapies (MDICT)

Cited by 65 publications

References 13 publications

Novel VEGF signalling inhibitors: how helpful are biomarkers in their early development?

Novel VEGF signalling inhibitors: how helpful are biomarkers in their early development?

Boundary Crossing Random Walks, Clinical Trials, and Multinomial Sequential Estimation

Making the Investigational Oncology Pipeline More Efficient and Effective: Are We Headed in the Right Direction?

Contact Info

Product

Resources

About